胱硫醚的反应Beta-Synthase (CBS) S-Adenosylmethionine (SAM): CBS基因突变的鉴定和功能分析高胱氨酸尿病人。
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门德斯MI, Colaco HG,史密斯德,拉莫斯RJ,流行,van Dooren SJ,塔瓦雷斯DE Almeida我Kluijtmans洛杉矶,詹森MC,里维拉,所罗门GS、莱安德罗P,布鲁姆HJ
胱硫醚的反应Beta-Synthase (CBS) S-Adenosylmethionine (SAM): CBS基因突变的鉴定和功能分析高胱氨酸尿病人。
J继承金属底座说。2014年3月,37 (2):245 - 54。doi: 10.1007 / s10545 - 013 - 9647 - 6。Epub 2013年8月23日。
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23974653 (在PubMed]
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减少了胱硫醚的反应beta-synthase (CBS)的变构激活S-adenosylmethionine (SAM)据报道,哥伦比亚广播公司高胱氨酸尿患者的功能障碍的原因。在这个工作我们的成纤维细胞进行了回顾性分析数据从62年高胱氨酸尿患者,发现13人打扰山姆激活。CBS基因型的背景被确认和相应的突变蛋白在大肠杆菌生产。在22个独立发现了九个不同的突变等位基因:这部小说突变p。K269del, p。P427L, p。S500L p.L540Q;和前面描述的突变p。P49L, p。C165Rfs * 2, p。I278T, p。R336H p.D444N。表达水平和残余酶活动,决定在大肠杆菌溶菌产物的可溶性分数,强烈的定位与氨基酸残基的影响。c端突变导致野生型的范围活动CBS和低聚物的形式迁移速度比四聚体,建议异常构象可能负责山姆激活的缺乏。 Mutations in the catalytic core were associated with low protein expression levels, decreased enzyme activities and a higher content of high molecular mass forms. Furthermore, the absence of SAM activation found in the patients' fibroblasts was confirmed for all but one of the characterized recombinant proteins (p.P49L). Our study experimentally supports a deficient regulation of CBS by SAM as a frequently found mechanism in CBS deficiency, which should be considered not only as a valuable diagnostic tool but also as a potential target for the development of new therapeutic approaches in classical homocystinuria.